Venous thromboembolism (VTE) is one of the leading causes of death in industrial countries. VTE is a multifactorial disease, and patients may have multiple risk factors simultaneously. Risk assessment is based on the identification of predisposing and triggering risk factors. A continuous decrease in VTE-associated mortality is attributed to the benefit from the improvement of the antithrombotic treatment with the wide use of LMWH and DOAC, as well as to the improvement of the monitoring of patients treated with VKA. Upon objective diagnosis, VTE evolves in three consecutive phases: (i) Acute or phase for 3–4 weeks from symptom onset; (ii) Primary treatment phase of VTE for the first 3–6 months after VTE diagnosis, and (iii) Secondary prevention phase of VTE. refers to long-term antithrombotic treatment to In selected patients at high risk of recurrent VTE, long-term antithrombotic treatment at therapeutic or lower doses is recommended. The aims of the antithrombotic treatment in patients with VTE are (i) the inhibition of the hypercoagulable state that led to thrombosis, (ii) the attenuation of the procoagulant activity of the fresh thrombus, (iii) decrease of the risk of thrombus extension and migration, (iv) the decrease of the risk of recurrence. Upon clinical suspicion, Prompt administration of therapeutic doses of rapidly acting antithrombotic agents (DOAC, LMWH, fondaparinux, or UFH) is mandatory. In selected patients at high risk of recurrent VTE, long-term antithrombotic treatment at therapeutic or lower doses is recommended.